1. Field of the Invention
The present invention relates to a nondestructive labeling method and a base sequence determination method for DNA or RNA.
2. Description of the Related Art
Among the known methods for analyzing DNA or RNA are the electrophoretic base sequence determination methods, such as the Maxam-Gilbert method and the dideoxy method. Even when the most sensitive radioisotope is employed as a detecting means in these methods, however, each trial run requires at least 1 pmol of the DNA or RNA. In addition, each of these methods involves a complicated preparation and determination procedure that requires several hours or longer for analysis. Accordingly, these methods are unsuitable for determining the base sequence of a DNA or RNA molecule having a large number of bases (for example, the entire human DNA or RNA chain).
In addition to the radioisotope and fluorescence methods, a method known as the heavy atom labeling method has been employed. See, for example, S. L. Commerford, Biochemistry, Vol. 10, page 1993 (1971). This method, however, does not aim to specifically label a particular individual, base, and therefore has not been developed as a base sequence determination method. Furthermore, a transmission electron microscope is required for the heavy atom labeling method, making it difficult to directly observe the labeled sample in or out of an aqueous solution.
Another method is described in Japanese Kokai No. 3-198798. A base sequence determination method for nucleic acids is disclosed that uses a scanning tunneling microscope (STM) or an atomic force microscope (AFM), depending upon a difference in electrical conductivity. However, base-specific labeling is not employed in this method.